P1409: PHASE-2 STUDY OF VARNIMCABTAGENE AUTOLEUCEL (IMN-003A) FIRST-IN-INDIA INDUSTRY CD19-DIRECTED CAR-T WITH FRACTIONATED INFUSIONS FOR PATIENTS WITH RELAPSED REFRACTORY B CELL MALIGNANCIES: IMAGINE STUDY
Authors: Pankaj Malhotra, Sharat Damodar, Sunil Bhat, Raja Thirumalairaj, Revathy Raj, Akshatha Nayak, Pooja Mallya, Ravi Joshi, Deepak Mb, Sudarshan Chougule, Sudeshna Dhar, Arun Kumar Mg, Pallavi Arasu, Sri Ramulu Elluru, Mohammed Manzoor Akheel, Anil Kamat
Journal: HemaSphere (2023)

Topic: 25. Gene therapy, cellular immunotherapy and vaccination - Clinical Background: Varnimcabtagene autoleucel (IMN-003A) is an autologous second-generation CAR-T cell product with a 4-1BB domain and A3B1 binder, non-FMC63 based murine single chain variable fragment targeting CD19, manufactured in India. Pre-clinical studies and phase 1 clinical trial in Spain has demonstrated potent in vitro, in vivo and clinical activity. Safety and efficacy results of IMAGINE phase 2 clinical trial for patients in India with relapsed/refractory B cell malignancies (CTRI/2022/03/041162) are presented here. Aims: Evaluate safety and efficacy of IMN-003A in patients with relapsed refractory B cell malignancies (B-ALL and B-NHL). Methods: Patients (pts) 3 to 45 years (B-ALL) and ≥ 18 years (B-NHL) with relapsed refractory B cell malignancies (RR BCM) were eligible if they had measurable disease, assessed by lymphoid blasts (B-ALL) or metabolic tumour bulk (B-NHL), received ≥1 prior regimen, refractory to last line of treatment with ECOG 0 to 1. Bridging therapy was allowed after apheresis. Flu-Cy lymphodepletion was used on days -5 to -3. Target dose was 1x106/kg CAR+ cells (B-ALL) and 5x106/kg CAR+ cells (B-NHL) (overall range 0.1x106 to 5x106), with fractionated infusions (10%/30%/60%). Primary objectives were overall response rate (ORR: CR + CRi in B-ALL and CR + PR in B-NHL) at day +90 after first infusion, and occurrence of adverse events including cytokine release syndrome (CRS) and/or Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Response was assessed by NCCN (B-ALL) and IWG (B-NHL) criteria; minimal residual disease (MRD) for B-ALL was analyzed by flow cytometry at 10-4 sensitivity and PET-CT for B-NHL. Adverse events (AEs) were graded using CTCAE v5.0. Results: At data cut-off, 22 pts (median age 31 yrs, range 3 - 66) with RR BCM (n=11 B-ALL; n=11 B-NHL) were enrolled. 18 pts received IMN-003A cells; 6 (33.3%) needed bridging therapy. Patient characteristics are described in Figure 1A. Median CAR-T cell manufacturing time was 14 days (range 10-27) with 100% manufacturing success. Median follow-up after IMN-003A administration was 97 days (range 3 - 284). Overall response rate (ORR) was 88.2% at D+28 (B-ALL 85.7%; B-NHL 88.8%) and 72.7% at D+90 (B-ALL 71.4%; B-NHL 75%). Two pts relapsed by D+90. Of MRD-evaluable pts, response was 100% at day+28 (n=7) and 83.3% at D+90 (n=6). Median time to first response was 28 days. Median progression-free survival (PFS, range 90-NR, Figure 1B) and overall survival (OS) were not reached (range 99-NR). AESIs reported were CRS (Grade [G] 1 70.5%; G3 + 5.9%; overall 76.4%); ICANS (G1 5.9%; G3 + 0%; overall 5.9%); neutropenia (G3 + 94.1%; overall 100%); anemia (G3 + 35.3%; overall 100%); and thrombocytopenia (G3 + 23.5%; overall 94.1%). CRS median onset was D+6 and duration 3 days. No G3+ ICANS was reported. Tocilizumab usage was in 41.2% (n=7/17) (majority for persistent G1 CRS). Treatment related mortality was 5.9% (n=1/17); 2 pts died of disease progression. IMN-003A cells demonstrated peak expansion on D+10 (range 7 – 21 days). 94% at D+28 and 36% at D+90 (range D+21 - NR) had measurable CAR+ T cells in peripheral blood. Updated results will be presented in the meeting. Summary/Conclusion: Varnimcabtagene autoleucel (IMN-003A) is a First-In-India Industry CD19-directed CAR-T Cell Therapy for RR BCM and has demonstrated excellent safety and efficacy outcomes with deep and durable responses including absence of severe neurotoxicity. This offers a significant benefit over standard treatment options for patients in India for RR BCM.Keywords: B cell acute lymphoblastic leukemia, Non-Hodgkin's lymphoma, Clinical trial, CAR-T